Department of Epigenetics, Medical Research Institute (MRI), Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Department of Pathology, School of Medicine, Tokai University, Isehara 259-1193, Japan.
Int J Mol Sci. 2023 Oct 4;24(19):14884. doi: 10.3390/ijms241914884.
Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that and (also known as () and ) are microglial genes that play important roles in the brain's innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of (also known as ). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: , and , responding to fungi, viruses and bacteria, respectively.
反转录转座子 gag 样（RTL）基因在真兽类胎盘和大脑中发挥着各种重要作用。最近已经证明， 和 （也称为 （）和 ）是小胶质细胞基因，通过去除双链 RNA 和脂多糖，分别在大脑对病毒和细菌的固有免疫中发挥重要作用。在这项工作中，我们研究了 （也称为 ）的功能。使用产生 RTL9-mCherry 融合蛋白的基因敲入小鼠，我们检查了 RTL9 在大脑中的表达及其对真菌zymosan 的反应。在这里，我们证明 发挥了重要作用，降解了大脑中的 zymosan。RTL9 蛋白定位于小胶质细胞溶酶体中，其中包含的 zymosan 被消化。此外，在表达缺乏 C 端逆转录病毒 GAG 样区的 RTL9ΔC 蛋白的 基因敲除小鼠中，zymosan 降解活性丧失。因此，RTL9 显然参与了这种反应，可能是通过其 GAG 样区。结合我们之前的研究，这一结果强调了三种源自逆转录病毒的小胶质细胞 RTL 基因作为当前大脑固有免疫系统的真兽类特异性成分的重要性： 、 和 ，分别对应真菌、病毒和细菌。
